dbSNP rs766898303: HDHD3:p.Val190Asp (chr9-113373786-A-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001304509.2(HDHD3):c.569T>A(p.Val190Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,612,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

HDHD3
NM_001304509.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.45

Publications

0 publications found

Variant links:

Genes affected

HDHD3 (HGNC:28171): (haloacid dehalogenase like hydrolase domain containing 3) Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

HDHD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.908

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304509.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDHD3	NM_001304509.2	MANE Select	c.569T>A	p.Val190Asp	missense	Exon 3 of 3	NP_001291438.1	Q9BSH5
HDHD3	NM_001304510.2		c.569T>A	p.Val190Asp	missense	Exon 3 of 3	NP_001291439.1	Q9BSH5
HDHD3	NM_001304511.2		c.569T>A	p.Val190Asp	missense	Exon 2 of 2	NP_001291440.1	Q9BSH5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDHD3	ENST00000374180.4	TSL:1 MANE Select	c.569T>A	p.Val190Asp	missense	Exon 3 of 3	ENSP00000363295.3	Q9BSH5
HDHD3	ENST00000238379.9	TSL:1	c.569T>A	p.Val190Asp	missense	Exon 2 of 2	ENSP00000238379.5	Q9BSH5
HDHD3	ENST00000900262.1		c.569T>A	p.Val190Asp	missense	Exon 4 of 4	ENSP00000570321.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000519

AC:

AN:

250422

AF XY:

0.0000517

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.0000618

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1460124

Hom.:

Cov.:

AF XY:

0.0000441

AC XY:

AN XY:

726026

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26058

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00

AC:

AN:

86144

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

1110748

Other (OTH)

AF:

0.0000166

AC:

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

M_CAP

Benign

0.067

MetaRNN

Pathogenic

0.91

MetaSVM

Uncertain

0.023

MutationAssessor

Pathogenic

3.0

PhyloP100

8.4

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-6.1

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.79

MVP

0.88

MPC

0.77

ClinPred

0.79

GERP RS

4.6

Varity_R

1.0

gMVP

0.95

Mutation Taster

=54/46

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over